BACKGROUND Mutations in the aggrecan(ACAN)gene are identified in patients with:spondyloepiphyseal dysplasia,Kimberley type;short stature with advanced bone age(BA);in the presence or absence of heterozygous ACAN mutat...BACKGROUND Mutations in the aggrecan(ACAN)gene are identified in patients with:spondyloepiphyseal dysplasia,Kimberley type;short stature with advanced bone age(BA);in the presence or absence of heterozygous ACAN mutation-induced early-onset osteoarthritis and/or osteochondritis dissecans;and spondyloepimetaphyseal dysplasia,ACAN type.Heterozygous mutations contribute to spondyloepiphyseal dysplasia,Kimberley type(MIM#608361),which is a milder skeletal dysplasia.In contrast,homozygous mutations cause a critical skeletal dysplasia,which is called spondyloepimetaphyseal dysplasia,ACAN type(MIM#612813).Lately,investigations on exome and genome sequencing have shown that ACAN mutations can also lead to idiopathic short stature with or without an advanced BA,in the presence or absence of early-onset osteoarthritis and/or osteochondritis dissecans(MIM#165800).We herein reported a heterozygous defect of ACAN in a family with autosomal dominant short stature,BA acceleration,and premature growth cessation.CASE SUMMARY A 2-year-old male patient visited us due to growth retardation.The patient presented symmetrical short stature(height 79 cm,<-2 SD)without facial features and other congenital abnormalities.Whole-exome sequencing revealed a heterozygous pathogenic variant c.871C>T(p.Gln291*)of ACAN,which was not yet reported in cases of short stature.This mutation was also detected in his father and paternal grandmother.According to the Human Gene Mutation Database,67 ACAN mutations are registered.Most of these mutations are genetically inheritable,and very few children with short stature are associated with ACAN mutations.To date,heterozygous ACAN mutations have been reported in approximately 40 families worldwide,including a few individuals with a decelerated BA.CONCLUSION Heterozygous c.871C>T(p.Gln291*)variation of the ACAN gene was the disease-causing variant in this family.Collectively,our newly discovered mutation expanded the spectrum of ACAN gene mutations.展开更多
The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by l...The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X<sup>2</sup> = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.展开更多
One of the most important aspects of interventional pulmonology is to obtain tissue or liquid samples of the chest to diagnose a respiratory disease;however,it is still possible to obtain insufficient tissue or cytolo...One of the most important aspects of interventional pulmonology is to obtain tissue or liquid samples of the chest to diagnose a respiratory disease;however,it is still possible to obtain insufficient tissue or cytologic specimens.Indeed,methylation detection is an effective method by which to establish a diagnosis.This review focuses on the clinical application of short stature homeobox 2 and RAS-associated domain family 1 subtype A DNA methylation detection in interventional pulmonology,including bronchoscopic fluid biopsy,transbronchial needle aspiration,and pleural effusion.展开更多
Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal(GI) cancers, most studies have focused on the function of non-HOX genes including c...Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal(GI) cancers, most studies have focused on the function of non-HOX genes including caudal-related homeobox transcription factor 1(CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers. HOXD10 is upregulated in colorectal cancer while it is silenced epigenetically in gastric cancer. Thus, it is essential to examine the differential expression pattern of various homeobox genes in specific tumor types or cell lineages, and understand their underlying mechanisms. In this review, we summarize the available research on homeobox genes and present their potential value for the prediction of prognosis in GI cancers.展开更多
NK2 genes (NKX2 gene cluster in humans) encode for homeodomain-containing transcription factors that are conserved along the phylogeny. According to the most detailed classifications, vertebrate NKX2 genes are classif...NK2 genes (NKX2 gene cluster in humans) encode for homeodomain-containing transcription factors that are conserved along the phylogeny. According to the most detailed classifications, vertebrate NKX2 genes are classified into two distinct families, NK2.1 and NK2.2 . The former is constituted by NKX2-1 and NKX2-4 genes, which are homologous to the Drosophila scro gene;the latter includes NKX2-2 and NKX2-8 genes, which are homologous to the Drosophila vnd gene. Conservation of these genes is not only related to molecular structure and expression, but also to biological functions. In Drosophila and vertebrates, NK2 genes share roles in the development of ventral regions of the central nervous system. In vertebrates, NKX2 genes have a relevant role in the development of several other organs such as the thyroid, lung, and pancreas. Loss-of-function mutations in NKX2-1 and NKX2-2 are the monogenic cause of the brain-lung-thyroid syndrome and neonatal diabetes, respectively. Alterations in NKX2-4 and NKX2-8 genes may play a role in multifactorial diseases, autism spectrum disorder, and neural tube defects, respectively. NKX2-1 , NKX2-2 , and NKX2-8 are expressed in various cancer types as either oncogenes or tumor suppressor genes. Several data indicate that evaluation of their expression in tumors has diagnostic and/or prognostic value.展开更多
目的对孤立性心房颤动(AF)患者进行垂体同型框2(PITX2)基因的突变扫描,并分析突变患者的相应临床特点。方法对160例孤立性AF患者和200名健康者的PITX2基因进行突变扫描。采用聚合酶链反应(PCR)扩增PITX2基因,通过单链构象多态性技术筛...目的对孤立性心房颤动(AF)患者进行垂体同型框2(PITX2)基因的突变扫描,并分析突变患者的相应临床特点。方法对160例孤立性AF患者和200名健康者的PITX2基因进行突变扫描。采用聚合酶链反应(PCR)扩增PITX2基因,通过单链构象多态性技术筛查突变,对发现异常的个体采用双脱氧核苷链末端合成终止法进行直接测序。采用Sequence scanner v 1.0软件分析测序图。结果在2例永久性AF患者中发现位于内含子区域的新改变g.766C>A、位于5’UTR区域的新改变g.8310C>T(c.-150C>T)。这两例携带者对药物及电复律治疗的反应较差,接受环肺静脉消融手术后,随访1年未再复发。200名健康者中未发现此改变。结论首次在中国孤立性AF患者中发现影响肺静脉肌袖发育基因PITX2的非编码区改变,其可能为我们进一步理解肺静脉肌袖在AF的发病过程中的作用提供新的启示。展开更多
目的:筛选上调尾型同源盒基因2(caudal type homeobox gene 2,CDX2)基因表达时人的胃癌细胞SGC-7901中差异表达的miRNA并预测其靶基因,并观察其对胃癌细胞生物学行为的影响.方法:提取瞬时转染48 h后空载体组(转染P E G F P-N1组)和转染...目的:筛选上调尾型同源盒基因2(caudal type homeobox gene 2,CDX2)基因表达时人的胃癌细胞SGC-7901中差异表达的miRNA并预测其靶基因,并观察其对胃癌细胞生物学行为的影响.方法:提取瞬时转染48 h后空载体组(转染P E G F P-N1组)和转染组(转染P E G F P-N1-C D X2组)细胞的总R N A,应用m i R N A芯片检测差异表达的miRNA,并通过Miranda、TargetScan、Mirtarget2软件预测其靶基因,通过Gene Ontology(GO)和KEGG pathway分析了解靶基因功能.CCK8法检测细胞增殖能力,划痕试验、Transwell小室、细胞黏附实验检测各组细胞体外迁移黏附能力.结果:PEGFP-N1-CDX2组较空载体组有59种差异表达的miRNA,其中25种miRNA发生2倍以上表达上调,34种miRNA发生2倍以上表达下调.通过Gene Ontology(GO)和KEGG pathway分析得到部分miRNA靶基因功能,这些靶基因参与了肿瘤的发生、发展、转移及预后.与对照组相比,PEGFP-N1-CDX2组的胃癌细胞生长、迁移和黏附能力均明显受到抑制(P<0.05).结论:上调CDX2基因表达可明显抑制人胃癌细胞SGC-7901的生长,抑制其迁移黏附能力,CDX2基因的抗肿瘤作用可能与miRNA有关.展开更多
文摘BACKGROUND Mutations in the aggrecan(ACAN)gene are identified in patients with:spondyloepiphyseal dysplasia,Kimberley type;short stature with advanced bone age(BA);in the presence or absence of heterozygous ACAN mutation-induced early-onset osteoarthritis and/or osteochondritis dissecans;and spondyloepimetaphyseal dysplasia,ACAN type.Heterozygous mutations contribute to spondyloepiphyseal dysplasia,Kimberley type(MIM#608361),which is a milder skeletal dysplasia.In contrast,homozygous mutations cause a critical skeletal dysplasia,which is called spondyloepimetaphyseal dysplasia,ACAN type(MIM#612813).Lately,investigations on exome and genome sequencing have shown that ACAN mutations can also lead to idiopathic short stature with or without an advanced BA,in the presence or absence of early-onset osteoarthritis and/or osteochondritis dissecans(MIM#165800).We herein reported a heterozygous defect of ACAN in a family with autosomal dominant short stature,BA acceleration,and premature growth cessation.CASE SUMMARY A 2-year-old male patient visited us due to growth retardation.The patient presented symmetrical short stature(height 79 cm,<-2 SD)without facial features and other congenital abnormalities.Whole-exome sequencing revealed a heterozygous pathogenic variant c.871C>T(p.Gln291*)of ACAN,which was not yet reported in cases of short stature.This mutation was also detected in his father and paternal grandmother.According to the Human Gene Mutation Database,67 ACAN mutations are registered.Most of these mutations are genetically inheritable,and very few children with short stature are associated with ACAN mutations.To date,heterozygous ACAN mutations have been reported in approximately 40 families worldwide,including a few individuals with a decelerated BA.CONCLUSION Heterozygous c.871C>T(p.Gln291*)variation of the ACAN gene was the disease-causing variant in this family.Collectively,our newly discovered mutation expanded the spectrum of ACAN gene mutations.
文摘The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X<sup>2</sup> = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.
文摘One of the most important aspects of interventional pulmonology is to obtain tissue or liquid samples of the chest to diagnose a respiratory disease;however,it is still possible to obtain insufficient tissue or cytologic specimens.Indeed,methylation detection is an effective method by which to establish a diagnosis.This review focuses on the clinical application of short stature homeobox 2 and RAS-associated domain family 1 subtype A DNA methylation detection in interventional pulmonology,including bronchoscopic fluid biopsy,transbronchial needle aspiration,and pleural effusion.
基金Supported by the Korean College of Helicobacter and Upper Gastrointestinal Research Foundation Granta Korea University Grant,No.K1512661
文摘Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal(GI) cancers, most studies have focused on the function of non-HOX genes including caudal-related homeobox transcription factor 1(CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers. HOXD10 is upregulated in colorectal cancer while it is silenced epigenetically in gastric cancer. Thus, it is essential to examine the differential expression pattern of various homeobox genes in specific tumor types or cell lineages, and understand their underlying mechanisms. In this review, we summarize the available research on homeobox genes and present their potential value for the prediction of prognosis in GI cancers.
文摘NK2 genes (NKX2 gene cluster in humans) encode for homeodomain-containing transcription factors that are conserved along the phylogeny. According to the most detailed classifications, vertebrate NKX2 genes are classified into two distinct families, NK2.1 and NK2.2 . The former is constituted by NKX2-1 and NKX2-4 genes, which are homologous to the Drosophila scro gene;the latter includes NKX2-2 and NKX2-8 genes, which are homologous to the Drosophila vnd gene. Conservation of these genes is not only related to molecular structure and expression, but also to biological functions. In Drosophila and vertebrates, NK2 genes share roles in the development of ventral regions of the central nervous system. In vertebrates, NKX2 genes have a relevant role in the development of several other organs such as the thyroid, lung, and pancreas. Loss-of-function mutations in NKX2-1 and NKX2-2 are the monogenic cause of the brain-lung-thyroid syndrome and neonatal diabetes, respectively. Alterations in NKX2-4 and NKX2-8 genes may play a role in multifactorial diseases, autism spectrum disorder, and neural tube defects, respectively. NKX2-1 , NKX2-2 , and NKX2-8 are expressed in various cancer types as either oncogenes or tumor suppressor genes. Several data indicate that evaluation of their expression in tumors has diagnostic and/or prognostic value.
文摘目的对孤立性心房颤动(AF)患者进行垂体同型框2(PITX2)基因的突变扫描,并分析突变患者的相应临床特点。方法对160例孤立性AF患者和200名健康者的PITX2基因进行突变扫描。采用聚合酶链反应(PCR)扩增PITX2基因,通过单链构象多态性技术筛查突变,对发现异常的个体采用双脱氧核苷链末端合成终止法进行直接测序。采用Sequence scanner v 1.0软件分析测序图。结果在2例永久性AF患者中发现位于内含子区域的新改变g.766C>A、位于5’UTR区域的新改变g.8310C>T(c.-150C>T)。这两例携带者对药物及电复律治疗的反应较差,接受环肺静脉消融手术后,随访1年未再复发。200名健康者中未发现此改变。结论首次在中国孤立性AF患者中发现影响肺静脉肌袖发育基因PITX2的非编码区改变,其可能为我们进一步理解肺静脉肌袖在AF的发病过程中的作用提供新的启示。
文摘目的:筛选上调尾型同源盒基因2(caudal type homeobox gene 2,CDX2)基因表达时人的胃癌细胞SGC-7901中差异表达的miRNA并预测其靶基因,并观察其对胃癌细胞生物学行为的影响.方法:提取瞬时转染48 h后空载体组(转染P E G F P-N1组)和转染组(转染P E G F P-N1-C D X2组)细胞的总R N A,应用m i R N A芯片检测差异表达的miRNA,并通过Miranda、TargetScan、Mirtarget2软件预测其靶基因,通过Gene Ontology(GO)和KEGG pathway分析了解靶基因功能.CCK8法检测细胞增殖能力,划痕试验、Transwell小室、细胞黏附实验检测各组细胞体外迁移黏附能力.结果:PEGFP-N1-CDX2组较空载体组有59种差异表达的miRNA,其中25种miRNA发生2倍以上表达上调,34种miRNA发生2倍以上表达下调.通过Gene Ontology(GO)和KEGG pathway分析得到部分miRNA靶基因功能,这些靶基因参与了肿瘤的发生、发展、转移及预后.与对照组相比,PEGFP-N1-CDX2组的胃癌细胞生长、迁移和黏附能力均明显受到抑制(P<0.05).结论:上调CDX2基因表达可明显抑制人胃癌细胞SGC-7901的生长,抑制其迁移黏附能力,CDX2基因的抗肿瘤作用可能与miRNA有关.
